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Timing, hosts and locations of (grouped) events of NanoImpactNet

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NanoSafetyCluster - Compendium 2012<br />

4. Improvement <strong>of</strong> analytical detection <strong>and</strong> labeling systems<br />

State-<strong>of</strong>-the-art: Existing analytical methods have detection limits<br />

that are too high to be able to reliably detect low concentrations<br />

<strong>of</strong> ENPs, despite their large surface area conferring a chemical<br />

reactivity equivalent to that <strong>of</strong> a much greater mass concentration<br />

<strong>of</strong> chemically identical, but larger-sized particles. Due to these<br />

limitations <strong>and</strong> challenges, which we face today when working<br />

with different ENP characterization techniques, almost nothing is<br />

known on the mobility <strong>of</strong> ENPs in natural environments.<br />

Progress: NanoValid will develop new approaches to increase<br />

precision <strong>and</strong> reproducibility <strong>of</strong> current analytical detection<br />

systems designed for nanomaterials at low concentration in<br />

biological <strong>and</strong> environmental samples, including methods to<br />

determine their chemistry, size <strong>and</strong> morphology, e.g. by advanced<br />

secondary electron <strong>and</strong> optical imaging <strong>and</strong> spectroscopic<br />

techniques. By using these improvements, NanoValid will also<br />

assess the applicability <strong>of</strong> a new system <strong>of</strong> respiratory exposure<br />

assessment that is based on mathematical turbulence models.<br />

State-<strong>of</strong>-the-art: Also information on reliability <strong>and</strong> comparability<br />

<strong>of</strong> current biodistribution <strong>and</strong> bioaccumulation data <strong>of</strong><br />

nanoparticles is scarce <strong>and</strong> severely affected by many factors, such<br />

as the status <strong>of</strong> tested nanomaterials, the labelling methods used<br />

<strong>and</strong> sample preparation from animal organs/tissues, which calls for<br />

st<strong>and</strong>ardized protocols for ENPs labelling, tracing <strong>and</strong><br />

quantification.<br />

Progress: NanoValid will develop reliable sample preparation <strong>and</strong><br />

isotope (radiogenic <strong>and</strong> stable) labeling protocols for selected<br />

ENMs, <strong>and</strong> related analytical protocols for reliably<br />

detecting/tracing various ENPs in different animal organs/tissues.<br />

3 Scope <strong>and</strong> objectives<br />

The main objective <strong>of</strong> NanoValid is the development <strong>of</strong> a set <strong>of</strong><br />

reliable reference methods <strong>and</strong> materials, including methods for<br />

dispersion control <strong>and</strong> the labeling <strong>of</strong> ENMs. Based on a<br />

comprehensive <strong>and</strong> critical literature <strong>and</strong> data survey, the most<br />

suitable test materials <strong>and</strong> methods are currently selected <strong>and</strong><br />

tested, <strong>and</strong> new nanomaterials will be synthesized, characterized<br />

<strong>and</strong> stabilized for final method validation.<br />

Already existing industrial or newly designed nanomaterials<br />

(ENMs) will be submitted to a comprehensive inter-laboratory<br />

validation campaign that includes the currently most advanced<br />

methods <strong>and</strong> instruments for measuring <strong>and</strong> characterizing <strong>of</strong><br />

ENMs, to generate accurate <strong>and</strong> reproducible material data <strong>and</strong><br />

st<strong>and</strong>ardized method protocols, also for labeling, tracing <strong>and</strong><br />

quantifying <strong>of</strong> nanoparticles in relation to their size/size<br />

distribution, morphology, material identification <strong>and</strong> other<br />

st<strong>and</strong>ard physicochemical (pc) properties. The stability <strong>and</strong><br />

behavior <strong>of</strong> selected ENPs will be monitored <strong>and</strong> tested in a variety<br />

<strong>of</strong> relevant biological <strong>and</strong> environmental samples <strong>and</strong> test media<br />

under both normal <strong>and</strong> extreme conditions to derive optimum <strong>and</strong><br />

reproducible fabrication, measurement <strong>and</strong> test conditions.<br />

The validated pc methods derived from the extensive<br />

intercalibration <strong>and</strong> inter-comparison <strong>of</strong> selected methods <strong>and</strong><br />

materials will be used to design well-defined reference materials,<br />

which in turn will be employed to validate, <strong>and</strong> where necessary<br />

adapt, modify <strong>and</strong> further develop current biological approaches<br />

(in vitro, in vivo <strong>and</strong> in silico) for assessing the toxicity <strong>of</strong> ENMs <strong>and</strong><br />

associated risks to human health <strong>and</strong> the environment. The effects<br />

<strong>of</strong> chronic exposure <strong>and</strong> <strong>of</strong> exposure under real-life conditions,<br />

where ENPs are likely to act as components <strong>of</strong> complex mixtures<br />

will be taken into account. Finally, appropriate reference methods<br />

will be established based on the validated pc <strong>and</strong> biological<br />

methods <strong>and</strong> their applicability assessed to a variety <strong>of</strong> industrially<br />

relevant ENMs by means <strong>of</strong> case studies.<br />

Specific objectives are to:<br />

(1) Test, compare <strong>and</strong> validate current methods to measure <strong>and</strong><br />

characterize physicochemical properties <strong>of</strong> selected ENMs<br />

(2) Monitor <strong>and</strong> control their dispersion <strong>and</strong> stability in various test<br />

media <strong>and</strong> environmental matrices by novel labeling methods<br />

(3) Generate panels <strong>of</strong> well-characterized <strong>and</strong> reproducibly<br />

synthesized ENMs, engineered nanoparticles (ENPs) <strong>and</strong><br />

associated products, designed for further (eco-) toxicological<br />

testing<br />

(4) Test, compare <strong>and</strong> validate current in vitro <strong>and</strong> in vivo methods<br />

(for toxicity <strong>and</strong> ecotoxicity testing) to early identify potential<br />

hazards, assess human health effects, including acute <strong>and</strong> chronic<br />

toxicity (oral, inhalation, dermal), <strong>and</strong> effects to the environment<br />

(5) Develop a st<strong>and</strong>ard test panel according to the mode <strong>of</strong> action<br />

<strong>and</strong> interaction <strong>of</strong> ENMs <strong>and</strong> ENPs with experimental media as<br />

used in OECD <strong>and</strong> other st<strong>and</strong>ardized tests<br />

(6) Identify responsive biomarkers for potential cytotoxic,<br />

genotoxic <strong>and</strong> immunotoxic effects<br />

(7) Develop further validated methods <strong>and</strong> materials to reference<br />

methods <strong>and</strong> materials, including Certified Reference Materials<br />

(CRMs), for more reliable risk <strong>and</strong> life cycle assessment (RA <strong>and</strong><br />

LCA)<br />

(8) Demonstrate feasibility <strong>of</strong> validated <strong>and</strong> established reference<br />

methods by means <strong>of</strong> case studies to assess <strong>and</strong> improve the<br />

performance <strong>of</strong> methods <strong>and</strong> systems both during normal<br />

operations <strong>and</strong> for management <strong>of</strong> accidental risks, evaluation <strong>of</strong><br />

risk reduction strategies <strong>and</strong> field detection systems, <strong>and</strong> for<br />

monitoring hazard <strong>and</strong> exposure to ENPs<br />

(9) Establish a database on hazard properties <strong>of</strong> selected ENPs that<br />

could be used to support the REACH hazard assessment system<br />

(10) Build a comprehensive knowledge hub <strong>and</strong> database to<br />

improve existing models on transport <strong>and</strong> fate <strong>of</strong> ENPs in the<br />

environment, including bioaccumulation, persistence,<br />

bioavailability <strong>and</strong> life cycle impacts onto all forms <strong>of</strong> biota<br />

(11) Initiate <strong>and</strong> support focused efforts to achieve international<br />

st<strong>and</strong>ardization in cooperation with national (e.g. DIN) <strong>and</strong><br />

international (e.g. OECD WGMN) organizations.<br />

4 Technical approach <strong>and</strong> work description<br />

NanoValid’s overall strategy is based on (1) a comprehensive <strong>and</strong><br />

critical review <strong>of</strong> the existing scientific literature <strong>and</strong> <strong>of</strong> relevant<br />

material databases, <strong>and</strong> on (2) a rigorous intercalibration campaign<br />

including outst<strong>and</strong>ing test laboratories in Europe <strong>and</strong> world-wide<br />

that participate in the project, to compare <strong>and</strong> validate current<br />

methods <strong>and</strong> test schemes that have been developed for hazard<br />

208 Compendium <strong>of</strong> Projects in the European NanoSafety Cluster

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